A question remains about the possible source of increased Th17 cells in HT patients. As an important proinflammatory mediator, leptin could stimulate the proliferation of T lymphocytes and promote the Th1 phenotype immune response [25]. Moreover, some recent studies indicate that leptin signalling controls the proliferation of CD4+CD25+ Treg cells through an autocrine pathway, because Treg cells produce higher levels of leptin and express high

leptin receptors www.selleckchem.com/products/INCB18424.html [22]. In agreement with this observation, significantly increased Tregs are found in both the leptin deficiency (ob/ob) and leptin receptor deficiency (db/db) mice; administration with the leptin blockade could delay the onset and progression of EAE, which shows an inverse correlation between the concentration of leptin and the percentage of Treg cells [15]. These

findings provide strong evidence that leptin signalling modulates a balance between effector T cells (Teff) and Treg cells. Because IL-6 plays an important role in regulating the balance between IL-17-producing Th17 cells and Tregs [26, 27] and the leptin signalling pathway shares the selleck chemical highest structural similarity and signalling capability with those of the IL-6-type cytokine receptors [5], we hypothesized that high levels of leptin may partly modulate Th17 cells involved in the pathogenesis of HT disease. In the present study, we provide direct evidence that plasma leptin and CD4+ T cell-derived leptin were higher in HT patients compared with

healthy controls. Neither the percentage of Th17 cells nor the level of Th17 cell-specific transcription factor RORγt correlated with plasma leptin, but the percentage of Th17 cells or the level of RORγt correlated positively with CD4+ T cell-derived leptin in HT patients. In addition, we have detected up-regulated levels of leptin, IL-17 and RORγt expression in TMCs from HT patients compared to a patient with simple goitre. To address a direct role of leptin in modulating Th17 cells, we found that neutralization of leptin decreases why Th17 cells in vitro. Together, our results provide direct evidence that T cell-derived leptin, but not plasma leptin, may contribute to the pathogenic role of increased Th17 cells in HT patients. Thus, further studies are warranted to characterize the molecular mechanism of leptin-mediated modulation of Th17 cells. This study was supported by National Natural Science Foundation of China (grant no. 30871193, 81072453, 30972748, 31100648, 30910103087), Health Department Foundation of Jiangsu Province (grant no.H200952), Graduate Student Research and Innovation Program of Jiangsu Province (CXLX11_0608, CXZZ12_0710), Jiangsu Province Qinglan Project and Top Talent Program of Jiangsu University. The authors have no financial conflicts of interest.